Ovarian cancer is the leading cause of death from gynecological malignancy in the US (1). Unfortunately, most cases are not diagnosed until the disease has progressed to stage III or IV, at which point recurrence is common even after an initially successful response to surgery and chemotherapy (2). It has been shown, however, that patients whose tumors are infiltrated with lymphocytes have a significantly higher 5-year survival rate than those who do not (3), suggesting the immune system plays an important role in combating tumor growth and that immunotherapy could be a successful strategy for fighting this disease. It is also known that many cancers are caused by viral infections.
The immune system plays an important role in controlling and preventing the growth of aberrant tumor cells via a mechanism known as “cancer immunoediting” (4). Cytotoxic CD8 T cells and natural killer (NK) cells can recognize and destroy these cells as they arise. It has been shown that immunodeficient mice lacking these cell types have increased susceptibility to tumor formation (4). However, tumor cells can develop mutations that help them evade detection by the immune system and mature tumors are therefore often poorly immunogenic, which has hindered the successful translation of many of these therapies to human patients (4). Additionally, tumors can form a unique microenvironment that shields them from direct contact with lymphocytes.
However, some advances have been made that are able to circumvent the tumor's immunosuppressive nature. The immunotherapeutic antibodies Ipilimumab and Nivolumab have recently been approved for the treatment of certain cancers. These checkpoint inhibitors target and block the activity of the immunosuppressive receptors CTLA-4 (Ipilimumab) and PD-1 (Nivolumab) on T cells. These drugs are not without safety concerns however, as these immune suppressive mechanisms are important for controlling potentially dangerous autoimmune and allergic reactions. Chimeric antigen receptor (CAR) T cell therapy has shown strong potential for treating blood-based cancers such as B cell acute lymphoblastic leukemia (ALL). To generate CAR T cells, the patient's own T cells are harvested and genetically modified to express a receptor that will recognize a specific surface antigen on the tumor cell (5). This method circumvents the signaling pathways that typically occur between the T cell and the antigen presenting tumor cell, rendering them resistant to immunosuppression. Because it requires genetic engineering of the patients own cells and due to potentially dangerous side effects of cytokine-release syndrome that can occur (6), CAR T therapy requires close individual monitoring that would not be necessary with more traditional drug therapies. The ability of CAR T cells to fight solid tumors such as ovarian cancer is still being evaluated.
Another method for fighting cancer that has shown potential is the use of oncolytic viruses (OVs) or viral vectors. These viruses are thought to act by specifically infecting and killing cancer cells. As cancer cells are lysed, dendritic cells are able to pick up released tumor antigens and generate a better anti-tumor immune response. However, the viruses and viral vectors were found to accumulate in the lymph nodes or other organs and at locations other than the intended target tumor. Thus, there remains a need to provide a method for safe and effective cancer treatment and prevention that does not have the danger and drawback as discussed above.